Prognosis of patients with axillary lymph node metastases from occult breast cancer: analysis of multicenter data.

PURPOSE: This study was conducted to evaluate prognosis of patients with level I/II axillary lymph node metastases from occult breast cancer (OBC). MATERIALS AND METHODS: Data of 53 patients with OBC who received axillary lymph node dissection (ALND) positive/negative (+/-) breast-conserving surgery between 2001 and 2013 were retrospectively collected at seven hospitals in Korea. The median number of positive lymph nodes (+LNs) was 2. Seventeen patients (32.1%) had >3 +LNs. A total of 48 patients (90.6%) received radiotherapy. Extents of radiotherapy were as follows: whole-breast (WB; n = 11), regional lymph node (RLN; n = 2), and WB plus RLN (n = 35). RESULTS: The median follow-up time was 85 months. Recurrence was found in four patients: two in the breast, one in RLN, and one in the breast and RLN. The 5-year and 7-year disease-free survival (DFS) rates were 96.1% and 93.5%, respectively. Molecular subtype and receipt of breast radiotherapy were significantly associated with DFS. Patients with estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) subtype had significantly lower 7-year DFS than those with non-ER-/PR-/HER2- tumor (76.9% vs. 100.0%; p = 0.03). Whole breast irradiation (WBI) was significantly associated with a higher 7-year DFS rate (94.7% for WBI group vs. 83.3% for non-WBI group; p = 0.01). Other factors including patient's age, number of +LNs, taxane chemotherapy, and RLN irradiation were not associated with DFS. CONCLUSION: Patients with OBC achieved favorable outcome after ALND and breast-targeting treatment. Molecular subtype and receipt of WBI was significant factors for DFS.

Surface Coating with Hyaluronic Acid-Gelatin-Crosslinked Hydrogel on Gelatin-Conjugated Poly(dimethylsiloxane) for Implantable Medical Device-Induced Fibrosis.

Polydimethylsiloxane (PDMS) is a biocompatible polymer that has been applied in many fields. However, the surface hydrophobicity of PDMS can limit successful implementation, and this must be reduced by surface modification to improve biocompatibility. In this study, we modified the PDMS surface with a hydrogel and investigated the effect of this on hydrophilicity, bacterial adhesion, cell viability, immune response, and biocompatibility of PDMS. Hydrogels were created from hyaluronic acid and gelatin using a Schiff-base reaction. The PDMS surface and hydrogel were characterized using nuclear magnetic resonance, X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, and scanning electron microscopy. The hydrophilicity of the surface was confirmed via a decrease in the water contact angle. Bacterial anti-adhesion was demonstrated for Pseudomonas aeruginosa, Ralstonia pickettii, and Staphylococcus epidermidis, and viability and improved distribution of human-derived adipose stem cells were also confirmed. Decreased capsular tissue responses were observed in vivo with looser collagen distribution and reduced cytokine expression on the hydrogel-coated surface. Hydrogel coating on treated PDMS is a promising method to improve the surface hydrophilicity and biocompatibility for surface modification of biomedical applications.

Outcome of breast-conserving treatment for axillary lymph node metastasis from occult breast cancer with negative breast MRI.

PURPOSE: We conducted this study to investigate the prognosis and failure pattern after breast-conserving treatment (BCT) in patients with occult breast cancer (OBC) with negative breast magnetic resonance imaging (MRI) (MRI-OBC). MATERIALS AND METHODS: Survival rates and failure patterns in 66 patients who received axillary lymph node dissection (ALND) and BCT for MRI-OBC between 2001 and 2013 at seven hospitals were analyzed. OBC was defined as adenocarcinoma in the axillary lymph node (ALN) +/- supraclavicular (SCN) or internal mammary lymph node (IMN) with a negative breast MRI. RESULTS: Fifty-four patients had only ALN metastasis (ALN only), and 12 patients had ALN metastasis along with SCN or IMN metastasis (ALN + SCN/IMN). Median follow-up was 82 months. The 5-year overall, disease-free, and breast cancer-free survival rates were 93.4%, 92.1%, and 96.8%, respectively. Nine patients experienced recurrence: breast (n = 4), regional lymph nodes (RLN, n = 1), distant metastases (DM, n = 2), breast/RLN (n = 1), and breast/RLN/DM (n = 1). Five-year disease-free survival was significantly higher in ALN only patients compared to ALN + SCN/IMN patients (96.1% vs. 75.0%; p = 0.02). CONCLUSIONS: Patients with MRI-OBC were successfully treated with BCT. There was a small risk of ipsilateral breast cancer recurrence. Failure patterns depended on the extent of initial disease.

Design and Methods of the Korean National Investigations of 70,000 Suicide Victims Through Police Records (The KNIGHTS Study).

OBJECTIVE: The suicide rate in South Korea was the second highest among the Organization for Economic Cooperation and Development countries in 2017. The purpose of this study is to understand the characteristics of people who died by suicide in Korea from 2013-2017 and to better prevent suicide. METHODS: This study was performed by the Korea Psychological Autopsy Center (KPAC), an affiliate of the Korea Ministry of Health and Welfare. According to the Korea National Statistical Office, the number of suicide victims nationwide was estimated to reach about 70,000 from 2013 to 2017. Comprehensive suicide records from all 254 police stations in South Korea were evaluated by 32 investigators who completed a 14-day didactic training program. Then, we evaluated the characteristics of suicide victims in association with disease data from the National Health Insurance Database (NHID), which is anonymously linked to personal information of suicide victims. RESULTS: Thirty-one of 254 police stations in the Seoul metropolitan area were analyzed by August 10, 2018. Findings showed that the characteristics of suicide victims differed according to the nature of the region. CONCLUSION: Our results suggest that different strategies and methods are needed to prevent suicide by regional groups.

Hypoxia-induced endothelial progenitor cell function is blunted in angiotensinogen knockout mice.

Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in tumor angiogenesis and associated with the pathogenesis of coronary atherosclerosis. This study was undertaken to determine the role played by AGT in endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was found that the number of EPC colonies formed by AGT heterozygous knockout (AGT(+/-)) cells was less than that formed by wild-type (WT) cells, and that the migration and tube formation abilities of AGT(+/-) EPCs were significantly lower than those of WT EPCs. In addition, the gene expressions of vascular endothelial growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial nitric oxide synthase (eNOS) were suppressed in AGT(+/-) EPCs. Furthermore, the expressions of hypoxia-inducible factor (HIF)-1α and -2α were downregulated in AGT(+/-) early EPCs under hypoxic conditions, suggesting a blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling pathways induced by VEGF, epithelial growth factor (EGF), or SDF-1α were suppressed in AGT(+/-) EPCs. In AGT(+/-) mice, the incorporation of EPCs into the tumor vasculature was significantly reduced, and lung tumor growth and melanoma metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced vasculogenesis.

Inhibitory effect of glyceollins on vasculogenesis through suppression of endothelial progenitor cell function.

SCOPE: Endothelial progenitor cells (EPCs) are derived from hematopoietic stem cells, and have the ability to differentiate into mature endothelial cells and contribute to neovascularization. Glyceollins are a type of phytoalexin produced in soybeans under stress conditions. The aim of this study is to determine the effect of glyceollin treatment on EPCs during early tumor vasculogenesis. METHODS AND RESULTS: We found that glyceollin treatment significantly decreased the number of EPC colony-forming units in human cord blood-derived AC133⁺ cells and mouse bone-marrow-derived c-Kit⁺/Sca-1⁺/Lin⁻ cells. Glyceollin treatment diminished the number of lineage-committed EPC cells in a dose-dependent manner (1-20 µM). Glyceollin treatment inhibited EPC migration, tube formation and the mRNA expression of angiopoietin-1 (Ang-1), Tie-2, stromal-derived factor-1 (SDF-1), C-X-C-chemokine receptor-4 (CXCR4), and endothelial nitric oxide synthase (eNOS) in cultured EPCs. Glyceollin treatment suppressed activation of Akt, Erk, and eNOS induced by SDF-1α or vascular endothelial growth factor (VEGF). Treatment with 10 mg/kg glyceollins significantly reduced the number of tumor-induced circulating EPCs and the incorporation of EPCs into neovessels in bone marrow transplanted mice. CONCLUSION: These results suggest that glyceollins inhibit the function of EPCs in tumor neovascularization. Glyceollins from soybean elicitation could be beneficial in prevention of cancer development via vasculogenesis.

Protective effect of rebamipide against Helicobacter pylori-CagA-induced effects on gastric epithelial cells.

BACKGROUND: Helicobacter pylori CagA dysregulates cell signaling pathways and leads to targeted transcriptional up-regulation of genes implicated in gastric cell injury. The aim of this study was to determine the effects of rebamipide on CagA-induced effects on gastric epithelial cells. We investigated the effects of rebamipide treatment (pre- or post-treatment before or after CagA transfection) on CagA-induced gastric cell injury. METHOD: We evaluated the morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization by confocal microscopy, IL-8 production by ELISA, and NF-κB activation by luciferase assay in AGS gastric epithelial cells and MDCK cells. RESULTS: Transfection of CagA into gastric epithelial cells induced morphologic changes (hummingbird phenotype), ZO-1 mislocalization, and IL-8 production in gastric epithelial cells. Pre-treatment with rebamipide inhibits CagA-induced effects on gastric epithelial cells, including morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization, IL-8 production, and NF-κB activity. CONCLUSIONS: These results suggest that rebamipide might have a potential role in the protection of H. pylori CagA-induced effects on gastric epithelial cells.

Does adjuvant radiotherapy suppress liver regeneration after partial hepatectomy?

PURPOSE: To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). METHODS AND MATERIALS: Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests at 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. RESULTS: The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 +/- 38.3cm(3) and 81.5 +/- 75.6cm(3), respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. CONCLUSIONS: In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.